The patient Wu completed treatment and was discharged from Tongji Hospital. [Photo provided to chinadaily.com.cn]
The 63rd American Society of Hematology Annual Meeting was successfully held on Dec 11-14, 2021. The meeting reported a series of newest breakthroughs in chimeric antigen receptor T-cell therapy. The five-year follow-up data updates of the single-arm phase II ZUMA-1 trial showed that the five-year overall survival rate was 42.6 percent among patients that have received CAR-T cell therapy. In recent years, CAR-T cell therapy has achieved great success in the field of lymphoma.
It is even challenging the supremacy of autologous stem-cell transplantation, which has been a key course of treatment for lymphoma in the past few decades. However, both ASCT and CAR-T have limitations. Many studies have indicated that CAR-T therapy and hematopoietic stem-cell transplantation have a complementary effect when used together, and can achieve better efficacy. For example, patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) have achieved better survival benefits after receiving ASCT combined with CAR-T therapy.
What benefits will be achieved with the combination of ASCT and CAR-T therapy?
ASCT is currently a critical treatment for lymphoma, but what would the efficacy be if it is combined with the promising CAR-T therapy?
Professor Zhou Jianfeng, director of the Department of Hematology at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, together with his team members, has applied the innovative combination of traditional autologous hematopoietic stem-cell transplantation with CAR-T therapy to the treatment of relapsed and refractory lymphoma.
The results of this groundbreaking clinical study were published last August in the core global hematology journal "Transplantation and Cellular Therapy". The study indicated that lymphoma develops a complex immunosuppressive microenvironment, which may prevent CAR-T from continuously targeting tumors. However, autologous hematopoietic stem-cell transplantation combined with high-dose chemotherapy can help CAR-T overcome this immunosuppressive microenvironment and promote the proliferation of CAR T-cells, thereby precisely killing cancer.
For lymphoma affecting the central nervous system in particular, the Department of Hematology of Tongji Hospital has led another clinical trial, specifically targeting in the long-term cure of patients in advanced stages and with CNS invasion after receiving the combined treatment of autologous hematopoietic stem-cell transplantation and CAR-T for the first time in the world. The results were published in the globally authoritative journal "Blood Cancer Journal". These results have received unanimous acclaim from medical institutions both at home and abroad and have drawn widespread attention. Subsequently, its efficacy and safety have been confirmed in many well-known blood disease centers.
In the past few decades, autologous hematopoietic stem-cell transplantation has played a fundamental role in the treatment of lymphoma. Therefore, the medical community expects that the combination of ASCT and CAR-T can bring more treatment options and benefits to patients with lymphoma.
Case sharing: Combination of ASCT and CAR-T therapy improves CNS lymphoma patient survival benefits
On Dec 21, Wu, a 52 years old woman, who suffered from DLBCL with multiple parts of the brain affected, received autologous hematopoietic stem-cell transplantation combined with CAR-T therapy at Tongji Hospital of Huazhong University of Science and Technology. She has since been discharged successfully.
Chief physician Meng Fankai, a member of the Tongji CAR-T therapy team, said, "As a typical case of lymphoma involving the central nervous system, Wu received six cycles of chemotherapy in the local hospital and developed memory impairment. She had tried alternative treatments, but with her condition deteriorating, she couldn't even recognize her family."
After a detailed evaluation, the team from the Department of Hematology of Tongji Hospital decided to adopt autologous hematopoietic stem-cell transplantation combined with CAR-T therapy for Wu. They collected stem cells and concurrently performed high-dose chemotherapy. After that, they infused autologous hematopoietic stem cells combined with sequential infusion of CAR T-cells. Wu's disease was quickly brought under effective control, and her cognitive abilities gradually returned to normal.
Professor Zhou Jianfeng said that autologous hematopoietic stem-cell transplantation can effectively break the immune barrier, help CAR-T drugs enter immune exempt organs, and offer precise efficacy. With large-scale promotion and application of this therapy in the future, it will be possible to offer new options to save patients suffering from lymphoma.
However, R/R DLBCL is still a common clinically challenging problem, especially in patients with refractory relapses that involve the CNS. With proper and personalized pretreatment for tumor reduction and effective control of the disease in the CNS, patients with CNS involvement are no longer problem in CAR T-cell therapy. Moreover, autologous transplantation combined with CAR T-cell therapy has a high complete remission rate, and the depth of remission is better than that of CAR T-cell therapy alone.
After receiving autologous transplantation combined with CAR-T therapy, patients with CNS involvement may overcome adverse prognostic factors and achieve good efficacy. The medical community is continuing to explore new treatments and strategies, hoping to improve the cure rate, prolong the survival period, and solve refractory recurrence through the application of individualized and precise treatments for different patients.
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